Download Molecule-Mimetic Chemistry and Mesoscale Self

Acc. Chem. Res. 2001, 34, 231-238
Molecule-Mimetic Chemistry and
Mesoscale Self-Assembly
NED B. BOWDEN, MARCUS WECK,
INSUNG S. CHOI, AND
GEORGE M. WHITESIDES*
Department of Chemistry and Chemical Biology, Harvard
University, 12 Oxford Street, Cambridge, Massachusetts 02138
Received April 24, 2000
ABSTRACT
Molecules are structured aggregates of atoms joined by chemical
bonds; crystals are aggregates of molecules, interacting covalently
or noncovalently. The work described in this Account uses molecules, crystals, and other forms of atomic/molecular matter to
suggest principles that can be used in generating structured
aggregates of millimeter-scale components, interacting through
capillary interactions. The properties of these aggregatessthat is,
their “chemistry”smimic aspects of the chemistry of molecules.
Molecule-Mimetic Chemistry
The study of atoms and molecules is the heart of chemistry. Scientists’ understanding of molecules, and of associated subjectssfrom covalent bonding to molecular
recognitionsis profound. The research we sketch here is
designed to test the proposition that principles learned
in studying moleculessprinciples with which we, as
chemists, are often so familiar that we take them for
grantedsare also useful in the design and “synthesis” of
nonmolecular systems. We suggest that it will be possible
to develop complex structures composed of “objects” that
self-assemble in processes that mimic (at least to some
extent) those by which molecules and molecular aggregates form, and that it will be possible to extend
concepts abstracted from the synthesis of molecules to
methods for the assembly of objects.
Chemistry is accustomed to mimicry as a strategy, and
often uses nature as a source of ideas: “biomimetic”,
“peptidomimetic”, “membrane-mimetic”, and related
phrases suggest that we accept the idea that understanding biology leads to abstract principles that can be used
to design nonbiological molecules.1,2 Chemists routinely
mimic principles of biological designshydrogen bonds for
directionality,3 hydrophobic effects to segregate molecular
surfaces from water,4 and shape complementarity to select
interacting partners5sfor other purposes.
Our program redirects the mimicry: instead of using
molecules to mimic other molecules, we use objects to
mimic molecules. Ideas such as phase segregation, chirality, hydrophobicity, shape recognition, and size exclusion
can be used to guide the self-assembly of these objects,
as they are used to guide the aggregation of molecules.
The structures that we wish to manipulate are built of
components that are larger than molecules, but too small
to be assembled conveniently by conventional meanss
sizes of a few nanometers to a few hundred micrometers
cover the range of interest. We have initially studied
componentssmillimeter- to centimeter-sized polymeric
polyhedra interacting with one another through capillary
forcesswith sizes a little above the upper end of this
range, because they embody most of the issues we wish
to explore, and because they are relatively easy to fabricate
and observe. This Account sketches our work in selfassembly of two- and three-dimensional arrays of small
objects through capillary forces, the chemical principles
that inspire this work, the molecular details that make it
possible, and possible uses for these processes and
assemblies.6-22
Mesoscale Self-Assembly (MESA)
Insung S. Choi was born in Sungjoo, South Korea. He received his B.S. and M.S.
degrees from Seoul National University (with E. Lee) and his Ph.D. degree from
Harvard University. He is currently a postdoctoral fellow working with R. Langer
at MIT.
Mesoscale Self-Assembly: The Self-Assembly of Objects
into Ordered Arrays through Noncovalent Forces. “Meso”
is a word that is used in two ways. It commonly means
“the middle”. For example, a mesomorph is a person of
medium stature, neither fat nor thin; the mesozoic era
was the time between the paleozoic and the cenozoic era.
More technically, and especially in physics, a mesoscale
object is one whose dimensions are comparable to the
scale of the phenomenon being investigated or the probe
being used to investigate it. For example, a quantum dots
a mesoscale object in electronics materialsshas dimensions of the order of the ballistic mean free path of an
electron (10-40 nm in a semiconductor at room temperature);23 a photonic band gap materialsa material that is
meso on the optical scaleshas periodic variations in index
of refraction that occur at scales comparable to the
wavelength of light (0.1-10 µm).24
George M. Whitesides received his A.B. degree from Harvard College in 1960,
and his Ph.D. from the California Institute of Technology with J. D. Roberts in
1964. He was a member of the faculty of MIT from 1963 to 1982, at which time
he joined the Department of Chemistry at Harvard University. His present research
interests include micro- and nanofabrication, self-assembly, complexity, and
biochemistry.
Millimeter-scale objects interacting through capillary
interactions extending over millimeter ranges also constitute a mesoscale system. This system, and self-assembly,
allow us to generate aggregates in ways that mimic some
molecular processes.6
Ned B. Bowden was born in Madison, Wisconsin. He received his B.S. degree
from Caltch in 1994 (with R. H. Grubbs) and his Ph.D. degree from Harvard in
1999. He is currently a postdoctoral fellow at Stanford University working with
R. M. Waymouth.
Marcus Weck was born in Berlin, Germany. He received his diploma from the
University of Mainz (working with H. Ringsdorf) and his Ph.D. degree in organic
chemistry from Caltech with R. H. Grubbs. He was a German Academic Exchange
Service postdoctoral fellow at Harvard. In 2000, he joined the faculty at Georgia
Tech as an Assistant Professor. His research interests include self-assembly,
supramolecular chemistry, polymer chemistry, and nanoscience.
10.1021/ar0000760 CCC: $20.00
Published on Web 12/21/2000
 2001 American Chemical Society
VOL. 34, NO. 3, 2001 / ACCOUNTS OF CHEMICAL RESEARCH
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Molecule-Mimetic Chemistry and Mesoscale Self-Assembly Bowden et al.
The Capillary Bond. A “bond” is an interaction between two objects that holds them together. In principle,
many different types of interactionsselectromagnetic,
hydrophobic, fluidic, photonic, capillary, and gravitationals
could be used to form bonds. In most of our work, we
have used capillary interactions to cause self-assembly.6
We suggest that the capillary interactions between
objects in our systems can be viewed as bonds that are
loosely analogous to chemical bonds. This analogy is not
an exact mapping from the molecular to the macroscopic,
but rather an aid to the imagination. There are at least
three similarities between capillary and chemical bonds.
(i) Both are reversible at some level of agitation or
temperature. (ii) Both interact through overlaps: of
menisci for capillary bonds, and of orbitals for chemical
bonds. (iii) Both are directional. There are, of course,
fundamental differences between capillary and chemical
bonds. (i) Capillary forces are described by classical
mechanics; chemical bonds require quantum mechanics.
(ii) Capillary and chemical bonds are described by potential curves with different forms. (iii) Capillary forces
can act over distances up to a millimeter; chemical bonds
act over distances of less than 1 nm.
The Opportunity: To Extend the Principles of
Molecular Self-Assembly to Mesoscale
(Micrometer- to Millimeter-Scale)
Self-Assembly
We wished to use ideas taken from molecular selfassemblysespecially shape-selective interactions between
hydrophobic surfacessto assemble objects larger than
molecules.1 There are a number of molecular processes
that are based on directional interactions and mating of
hydrophobic surfaces: examples include DNA/DNA duplex formation,25 receptor/ligand association,26 π-π stacking,27 formation of self-assembled monolayers (SAMs),28
molecular recognition,29 formation of molecular crystals,30
and folding of proteins.31 All are processes that might be
mimicked using MESA. By studying experimentally welldefined, nonmolecular, self-assembling systems, we also
hope to learn principles that might be useful in understanding self-assembling molecular systems.
Previous Work in MESA
In most previous examples of MESA, spherical objects
(from nanometer-sized proteins and colloids to micrometer-sized latex spheres) have formed close-packed arrays;
the interactions involved have included chemical,32-34
electrohydrodynamic,35 capillary,36-41 shear,42 dipolar,43
electrostatic,42,44 light-based,45 entropic,46 magnetic,44,47
and gravitional.43 These systems are interesting for their
ability to show self-assembly, but they are limited in the
range of structures they can generate. One goal of our
work, as with organic synthesis, is to develop flexible
strategies leading to a range of structures. Our strategy is
to design and fabricate nonspherical objects with patterned surfaces that direct the capillary interactions.
232 ACCOUNTS OF CHEMICAL RESEARCH / VOL. 34, NO. 3, 2001
FIGURE 1. Six examples of systems that minimize the area of a
high energy surface. (a) Water spreading on a SAM terminating in
carboxylic acid groups. (b) Two drops of benzene in water coalescing into one drop. (c) A receptor with a hydrophobic area interacting
with a hydrophobic ligand. (d) Water rising in a capillary to coat the
high-energy glass surface. (e) Two objects floating at the PFD/H2O
interface interacting through lateral capillary forces to minimize the
surface area at the interface. (f) Two objects with one face
hydrophobic and coated with a hydrophobic liquid or liquid metal
and suspended in water coming into contact. In both systems (e
and f) the objects can move laterally with respect to the one another
to maximize the overlap of their faces. The thick black lines indicate
hydrophobic surfaces, and the thin lines indicate hydrophilic
surfaces.
Bonds: Capillarity, the Hydrophobic Effect,
Surface Tension, and Interfacial Free Energy
Capillary interactions have five attractive characteristics.
(i) The characteristic decay length for lateral capillary
forces is in the right rangesfrom nanometer to millimeter,
depending on the dimensions of the objectssto be useful
with objects of the size (micrometer to centimeter) that
we wished initially to explore. (ii) The strength of the
capillary interactions can be adjusted to be comparable
to the strength of the shear forces that are used to disrupt
the aggregation. (iii) Capillary interactions can be used
to assemble either 2D or 3D arrays. (iv) Capillary interactions are well understood conceptually (although their
numerical analysissusing the Laplace equationsis often
intractably complicated). (v) Designs of the surfaces that
generate the menisci allow the capillary interactions to
be made directional.
It is useful to understand the molecular basis of
capillary interactions. Capillarity, surface tension, and the
hydrophobic effect all reflect the same phenomenonsthat
is, the tendency of a system containing water or other
liquids to minimize its interfacial free energy, usually by
minimizing the area of the interface with the highest free
energy (Figure 1). Molecules of a polar liquid or solid at
an interface with a less polar phase (air, nonpolar polymer,
Molecule-Mimetic Chemistry and Mesoscale Self-Assembly Bowden et al.
hydrophobic molecular interface) are less stable than
those in the bulk. A system will thus tend to minimize
the area of its exposed, high-energy interfaces. The
spreading of a drop of water on a carboxyl-terminated
SAM covers the surface with the highest surface free
energy (that of the SAM), albeit at the expense of increasing the area of the water/air interface (Figure 1a). Coalescence of drops of benzene suspended in water, association of a hydrophobic ligand with a hydrophobic active
site, and rise of water in a capillary all reflect changes in
areas of interfaces that minimize interfacial free energies
(Figure 1b-d).
The Design of Components for MESA
We describe two systems that generate ordered arrays of
objects using MESA (Figure 1e,f). The first uses lateral
capillary interactions to assemble millimeter-scale plates
floating at the interface between perfluorodecalin (PFD)
and water (Figure 1e).6-9,16-22 The second also uses capillary forces (involving either a hydrophobic liquid or liquid
metal) to direct the self-assembly of polymeric polyhedra
(micrometer to centimeter in size) suspended in water into
3D aggregates (Figure 1f).10-15
Use of Polyhedral Components with Patterned Faces
Allows the Capillary Interactions To Be Directional. To
achieve structural complexity in 2D structures formed at
the H2O/PFD interface using capillary interactions, these
interactions must be directional. The faces of the objectss
small, polymeric platesswere patterned into hydrophobic
and hydrophilic sets and regions. The hydrophobicity of
the faces, and the arrangement of the faces on the object,
determined the shape of the menisci and the directionality
and strength of the capillary interactions.
The strongest capillary interactions between the objects
were those that resulted in the largest decrease in interfacial free energy when the components came togethers
that is, as a first approximation, to the best matching of
the contours of their menisci. This principlesdesigning
the overlap of menisci to achieve strong capillary bondings
has an obvious if imprecise analogy to using the overlap
of electronic orbitals to achieve strong molecular bonding
(Figure 2a).
Nomenclature Describing the Number and Location
of the Hydrophobic Faces, and the Sense of the Menisci.
The lateral motion of the two plates shown in Figure 1e
involving menisci of the same sense (i.e., two positive or
two negative menisci) lowers the surface area of the PFD/
H2O interface and thus lowers the free energy of the
system. The lateral capillary forces move the plates toward
or away from one another; the vertical capillary forces
move the plates out of or into the interface. In 3D MESA,
two faces coated with a hydrophobic liquid or liquid metal
and suspended in water come into contact and reduce
the surface area of the hydrophobic liquid/water interface.
In all figures, the dark faces on the drawings of the
objects and the thick lines indicate hydrophobic faces; the
light faces and thin lines indicate hydrophilic faces. For
the objects in the 2D system, we number the hydrophobic
FIGURE 2. (a) The contours of the menisci (indicated by dashed
lines) on two hexagons change as the hexagons approach one
another. (b) Two positive menisci (those rising above the interface)
pull the objects toward one another, two negative menisci (those
sinking below the interface) pull the objects toward one another,
and a negative meniscus repels a positive meniscus. (c) The
contours of the menisci on various objects at the PFD/H2O interface
in 2D MESA. The top drawings are the top views of the objects, the
middle drawings are the side views of the objects, and the bottom
drawings are views of the contours of the menisci.
faces by placing the number of those faces in a square
bracket. For example, we call a hexagon with two adjacent
hydrophobic faces a [1,2] hexagon, and a hexagon with
every other face hydrophobic a [1,3,5] hexagon.
In Figures 3-8, we show optical or scanning electron
micrographs of the assemblies and schematic representations of the assemblies to aid the eye (the micrographs
have scale bars and, thus, can be easily distinguished from
the computer-drawn schemes). These micrographs show
some of the best assemblies. The schematic representations of the assemblies are next to the micrographs and
show the pattern of the hydrophobic and hydrophilic faces
and, in some cases, how the objects were assembled into
the arrays.
Engineering the Capillary Bond by Controlling the
Shapes of Menisci. We wished to control the shapes of
the menisci, to generate capillary bonds with different
strengths. The better the match between contours of two
menisci, the greater the reduction in the area of the PFD/
H2O interface as the two interacting plates come together,
and the stronger the capillary bond. With this understanding, we designed a range of face structures that would test
the strength and selectivity of the bonds.6,7 The objective
of this work was, in a sense, to begin to develop a “periodic
table”sa set of plates having edges patterned to generate
menisci with shapes and symmetries that would result in
selective interactions. We used four strategies in 2D MESA
(Figure 2c). That is, we patterned (i) the location of the
hydrophobic faces so that the plates were tilted at the
PFD/H2O interface; (ii) the hydrophobic areas on the faces
to be chiral (faces of opposite chirality interacted more
strongly than those with the same chirality); (iii) the faces
into vertical hydrophobic stripes; and (iv) the horizontal
profile of the faces.
Similar methods were used in some of the 3D systems.
Here, the hydrophobic patches were in the form of
triangles, squares, and other geometric figures. The most
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Molecule-Mimetic Chemistry and Mesoscale Self-Assembly Bowden et al.
stable pair formed between faces that had hydrophobic
patches that matched when juxtaposed.
Experimental Investigations of MESA:
Two-Dimensional Assemblies
Methods. The objects used in the two-dimensional assembly were readily fabricated from poly(dimethylsiloxane) (PDMS). PDMS is hydrophobic (the advancing contact angle of water θaH2O ≈ 108°) but can be made
hydrophilic by oxidation in an oxygen plasma (θaH2O <
30°). Most objects used in these examples had densities
of F ) 1.05 g/cm3. These plates float with their center of
gravity well above the PFD/H2O interface; the interactions
between positive menisci at the hydrophobic faces thus
dominate assembly. Faces that were to remain hydrophobic were protected from oxidation by tape or a temporary
protective film (we often used correction fluid). The
objects were agitated in a dish with PFD and H2O on an
orbital shaker; typical conditions were agitation at an
orbital frequency, ω, of ω ) 1.5 s-1 for 30 min. The faster
the rotation, the stronger the shear forces opposing
assembly.
Hexagonal Plates. Many of our studies of twodimensional assemblies used components with a common
hexagonal shape, and with edges functionalized to be
hydrophobic or hydrophilic.6-8 We have examined all
permutations (14 in all) of these edge-functionalized
plates. This survey established a number of basic principles of MESA. (i) As expected, aggregates usually form
in a way that juxtaposes hydrophobic edges. (ii) Plates with
a noncentrosymmetric distribution of edges are tilted
relative to the interface. This tilt can strongly influence
the form of the aggregate. (iii) The menisci extend for
several millimeters, and objects interact over this distance.
(iv) The directionality and strength of interactions can be
controlled by the design of the hydrophobic patterns;
these interactions determine the structures of the aggregates in a predictable way. (v) The agitation of the
assemblies occurs primarily by shear; increased agitation
gives smaller aggregates but does not influence the
structure of the aggregate. (vi) The assembly of the objects
is reversible; objects with menisci that do not match
dissociate more rapidly than those with menisci that
match. (vii) Appropriate design gives edges that are
selective in their interactions. (viii) The capillary interactions can be modeled to some degree by finite element
simulation.
The [1] hexagons assembled into dimers, and the [1,3,5]
and [1,2,4,5] hexagons assembled into open, hexagonal
arrays (Figure 3). The trimers formed by [1,2] hexagons
were strongly tilted (by 14°) relative to the plane of the
PFD/H2O interface: this tilt reflects the noncentrosymmetric distribution of vertical capillary forces.
Hierarchical Self-Assembly. Because good matches of
the contours of menisci resulted in strong capillary bonds,
it was possible to design patterns of hydrophobic edges
that showed strong selectivity (Figure 4a).8 The two objects
(1 and 2) had the same area of hydrophobic face, but the
234 ACCOUNTS OF CHEMICAL RESEARCH / VOL. 34, NO. 3, 2001
FIGURE 3. (a) [1] Hexagons assembled into dimers based on the
attraction between the hydrophobic faces. (b and c) Both [1,3,5] and
[1,2,3,4] hexagons assembled into open hexagonal arrays. Optical
micrographs are shown on the left side, and schematic representations on the right side.
FIGURE 4. (a) Objects assembled to match the hydrophobic areas
on each face. (b) Arrays formed by chiral hydrophobic patches. The
dark triangular patches in the hexagons and triangles on the righthand side of the figure indicate the pattern of the hydrophobic
patches on the faces. (c) An extended hierarchical array. Optical
micrographs are shown on the left side, and schematic representations on the right side.
menisci on 1 matched those on 2 poorly: as a result, both
1 and 2 formed homo-oligomers separately, but 1 did not
form a stable hetero-oligomer with 2. Chiral hydrophobic
edges gave a more subtle selectivity.8 The areas of the
hydrophobic edges of 3 and 4 were the same, but both
were chiral and of the opposite chirality. Association of 3
Molecule-Mimetic Chemistry and Mesoscale Self-Assembly Bowden et al.
FIGURE 6. Self-assembled electrical network with parallel connectivity. (a) The basic pattern of copper dots, wires, and contact
pads used. (b) A single patterned polyhedron prior to assembly. (c)
A photograph of the assembled aggregate on top of a penny. The
aggregate is connected to a battery via an isolated pair of wires.
This lights up the six LEDs that are connected to each other in
parallel. (d) An electrical circuit diagram showing the parallel network
formed. The gray circles show the 12 polyhedra, and the LEDs are
shown in black. Assembly results in the formation of 16 pairs of
wires that consist of the red, green, and blue pairs.
stable arrays; (ii) solder connections constitute a step
toward electrically functional, self-assembling systems.
The 3D arrays were intrinsically more stable than the twodimensional arrays, since each object is held in its place
in the lattice by more contacts.
FIGURE 5. (a and b) Two examples of crystalline three-dimensional
arrays. Self-assembly was accomplished by agitating the pieces in
an aqueous KBr solution at 60 °C using molten alloy as adhesive.
After completion of the self-assembly, the suspension was allowed
to cool to room temperature, where the alloy solidified resulting in
a stable structure. (c) Objectss10 µm in widthsassembled into
crystalline arrays. The schematic representations of the objects are
shown on the left side. The dark faces are hydrophobic, and the
light faces are hydrophilic. The optical micrographs (a and b) and
the scanning electron micrograph (c) on the right side show
examples of the assemblies.
with 4 occurred readily; association of 3 with 3, or 4 with
4, did not (Figure 4b).
Figure 4c demonstrates hierarchical self-assembly using
mesoscale objects.9 This assembly used two different
PDMS objects containing concave and convex hydrophobic faces with complementary shapes. The capillary
interactions between concave and convex hydrophobic
faces are the strongest; the weakest interactions occur
between two concave hydrophobic faces.
Three-Dimensional Assemblies
Conceptually, 3D systems are similar to the 2D system,
although operationally somewhat different. To generate
3D assemblies, we coated selected faces of polyhedra with
a hydrophobic liquid or low-melting liquid solder. The
resulting polyhedra were agitated in suspension in an
isodense medium. Capillary interactions pulled the liquidcoated faces together when they came into contact (Figure
1f).10-15 Large, extended crystalline arrays formed from
appropriately functionalized polyhedra (Figure 5a,b).11,15
We used liquid metal for two reasons: (i) it has a high
interfacial free energy with water (∼400 mN m-1) and gave
New Materials and New Functional Systems
by MESA
Many of the assemblies we have described here could be
as easily assembled by hand as by self-assembly. The
design and fabrication of these assemblies are intellectually stimulating and important for what they teach about
the self-assembly process. These assemblies do not,
however, provide a new capability to fabrication or
synthesis. To be useful, MESA must offer strategies that
generate aggregates that could not be made by conventional means. Two examples are the self-assembly of
small, nonspherical objects (e10 µm) into ordered arrays
and the self-assembly of objects into functional systems.
3D Assemblies of 10-µm Scale Components. The
challenge in applying MESA to submillimeter-sized objects
is the fabrication of the polyhedral components with faces
appropriately patterned. We have developed a combination of photolithography, electrochemistry, and metal
evaporation that allows the fabrication of hexagonal plates
(10 µm in size) in which the top and bottom faces are
patterned independently of the side faces. These plates
aggregate into ordered arrays, after hydrophobic faces are
coated with a hydrophobic prepolymer (Figure 5c).13 We
believe that with development, this strategy in 3D MESA
will provide a route to photonic band-gap materials.
Assemblies of Functional Arrays. We have successfully
constructed small, 3D electrical networks (Figure 6).14,15
Patterns of solder on the faces of polyhedra both held the
polyhedra together (by capillarity) and made electrical
connections between them.15 Light-emitting diodes (LEDs)
incorporated into the system traced the electrical circuits.
Figure 6 shows a photograph of an assembled electrical
VOL. 34, NO. 3, 2001 / ACCOUNTS OF CHEMICAL RESEARCH 235
Molecule-Mimetic Chemistry and Mesoscale Self-Assembly Bowden et al.
FIGURE 7. (a) Hexagons coating a drop of water in heptane. (b)
The drops are stable even when pressed together.
network containing LEDs connected with parallel connectivity; we have also generated serial networks. These
experiments are a first step toward the self-assembly of
3D microelectronic systems.
Models of Supramolecular Aggregates. We have developed a system that illustrates MESA on the surface of
a spherical drop.16 Small drops of one liquid were suspended in a second, immiscible liquid (chlorobenzene in
H2O, perfluorodecalin in H2O, or H2O in heptane). Hexagonal rings (100 µm in length, fabricated from electroplated gold) were added and self-assembled on the surface
of the droplet (Figure 7). The hexagonal rings could be
fabricated with the bottom and side faces hydrophobic
and the top face hydrophilic, or vice versa; these rings
floated at the interface of the two fluids. The hexagons
stabilized the drops: two drops covered with hexagons
would not fuse when pressed together (Figure 7b). Capillarity held the hexagons on the surface of the drop.
Mesoscale Biomimetic Systems. One of the most
stimulating applications of MESA is the abstraction of
important concepts in biological systems, and their use
to join mesoscale objects. Several biological phenomenas
ligand/receptor interactions,18 DNA/DNA duplex formation,19 and protein folding20shave already served as the
basis for strategies for self-assembly. These systems use
simple shapes interacting through simple interactions; as
such, they may provide tests for computer models of
biological systems and suggest new strategies for precision
assembly.
Figure 8a shows the results of shape-selective recognition of a chiral object by a chiral cavity. The receptors
(the larger objects in the picture) showed high selectivity
in recognition of the ligands based on chirality. Figure 8b
describes a system modeled on sequence-specific molecular recognition in DNA and RNA. The strands were made
of sequences of four objects chosen to be analogues of
the purine and pyrimidine bases of nucleic acids and
connected via a flexible PDMS thread. When the smaller
strand self-assembled with its complementary sequence
along the longer strand, the array was stable. Other
configurations were less stable and broke apart under
agitation.
Conclusions
Molecule-Mimetic Chemistry. Chemistry builds complex
structures using atoms as bricks and bonds as mortar. Can
236 ACCOUNTS OF CHEMICAL RESEARCH / VOL. 34, NO. 3, 2001
FIGURE 8. Self-assembled structures based on (a) shape-selective
recognition and (b) sequence-specific recognition between a 22membered single strand and a seven-membered probe. The
representations of the objects are shown above the optical
micrographs of the assemblies.
chemistry start from its experience with atoms and
molecules and build a new “chemistry” using different
components and connectors? We believe that the answer
to this question is “yes” and have used the system
comprising millimeter-scale objects and capillary interactions as a demonstration. The advantage of this system is
that it is relatively easy to “design” the characteristics of
capillary bonds; the corresponding characteristics of
atomic/molecular bonds are fixed by the structure of the
atoms and cannot be influenced by the chemist. Structures assembled from large components also have the
attractive characteristic that determination of structure
can be accomplished by the eye. The disadvantages of
these systems are that the number of particles that can
be observed is small, that the encounter frequency of their
components is very low relative to atomic/molecular
systems, and that their complexitysrelative to the complexity generated by the many types of bonds that can
form between the many elements of the periodic tables
is also low. Still, it is a start, and by working with
microfabricated components and by extending capillary
interactions, or by supplementing them with electrical or
magnetic interactions,21 it will certainly be possible to
build more complex systems.
What is the value of this exercise? Why is it different
from playing with a child’s building toys? We submit that
there are several reasons for pursuing it. First, it is
instructive and intellectually engaging to consider bonds
and bonding abstractly, and to ask what principles can
be taken from them and embedded in nonatomic/molecular systems. In this sense, MESA is engaging in the
same sense that “biomimetic” studies involving molecules
are engaging: biomimetic studies often do not imitate
biology very closely, but they do suggest new principles
of design. Second, building and fabricationsthe assembly
Molecule-Mimetic Chemistry and Mesoscale Self-Assembly Bowden et al.
of simple structures into complex onessare among the
most fundamentals of human activities, and new approaches to them are always interesting (and potentially
useful). Third, and especially as the components become
smaller, these methods will provide routes to structures
that cannot be fabricated by other methods. True, the
structures are not molecular, but the concepts are, and
in any event, chemistry should have an expansive vision
of its domain.
Molecular Chemistry Presently Has More To Offer to
MESA Than MESA Does to Chemistry. MESA has been
stimulated by chemistry, but the complexity of most
chemical systems is too high to realize in a mesoscopic
model. Chemistry, however, contributes to MESA in many
ways: (i) through molecular control of surface chemistry
and surface properties; (ii) through control of bulk
propertiessmagnetic susceptibility, dielectric constant,
density, and porositysof the components; (iii) by providing phenomena to mimic; (iv) by providing routes for
fabrication of nanometer- to millimeter-scale components,
and (v) by providing possible molecular interactions for
the forces between objects.
Toward Possible Applications. For MESA to be useful,
the sizes of the components must be smaller (1-100 µm)
and/or the assemblies must be functional. In related work
by Nagayama et al., nanometer- and micrometer-sized
spheres were assembled into close-packed arrays through
lateral capillary forces.48,49 This work demonstrates that
capillary forces can be used to assemble objects as small
as 25 nm into arrays. We do not yet know whether the
capillary forces will still be directional on that size scale,
although we do know from our work that objects with
dimensions of 10 µm interact through directional capillary
interactions.13 The fabrication of objects on this size scale
will continue to be a challenge, and new techniques for
fabrication will be welcome.
Function can take a broad range of forms. The assemblies can be functional as models for systems to study
(such as models of molecular and biological systems), or
as structures that can act as components in devices
(microelectronic, photonic, MEMS). Although there are no
current commercial examples of functional devices fabricated by MESA (aside from those generated by fluidic
self-assembly),50,51 MESA has several characteristics that
make it an attractive option for fabricating nanometerand micrometer-sized arrays: (i) it can result in excellent
registration between objects. (ii) It is error-correcting in
the sense that misassembled arrays are relatively unstable.
(iii) It is compatible with a variety of materials. (iv) It can
generate electrical connections. (v) It generates structures
with the right size for photonic band-gap materials,
waveguides, MEMS, and high surface area catalysts. The
direction of MESA will be decided in part by how small
the components can be made, and in part by the kinds of
structures that can be assembled from them.
This research was supported by the NSF (CHE-9122331; CHE9901358) and NIH (GM-30367). N.B.B. acknowledges a predoctoral
fellowship from the Department of Defense. M.W. thanks the
German Academic Exchange Service (DAAD) for a postdoctoral
fellowship.
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